Immunotherapy has great promise in improving malignant tumor treatment.However,the efficacy of existing strategies is often limited by the immunosuppressive environment.Here,we demonstrate an in situ bionic immunoacti...Immunotherapy has great promise in improving malignant tumor treatment.However,the efficacy of existing strategies is often limited by the immunosuppressive environment.Here,we demonstrate an in situ bionic immunoactivator,PLT-Bec1/DTA-1,with possessed natural advantages of platelets for tumor recruitment and activation,on which DTA-1(CD357 monoclonal antibody)and Bec1 were tethered as combined immune boosters.PLT-Bec1/DTA-1,as a self-triggered release repository,can deliver the pre-tethered Bec1 and DTA-1 deeply through the secretion of platelet microparticles(PMPs),thereby cooperate tacitly and exhibit superiority in immune activation of dendritic cells(DCs)and T cells via autophagy inducibility,coupled with glucocorticoid-induced tumor necrosis factor receptor(GITR)-triggered T_(Reg) suppression,remodeled the immunosuppressive network of tumor microenvironment.PLT-Bec1/DTA-1 promoted antigen presentation and T cell proliferation,and alleviated the low activity state of bone marrow-derived dendritic cells(BMDCs)in tumor suppressive environment.PLT-Bec1/DTA-1 inhibited tumor recurrence(5-and 13-fold lower of control group in tumor volume)and CD8^(+)T/T_(Reg) ratio(6.3-and 8.8-fold vs.control group)in mouse tumor model after intravenous or subcutaneous administration.Also,PLT-Bec1/DTA-1 prevented tumor colonization in lung through in situ immune activation,and was slightly superior to the combined of Bec1 and PD-L1.Our findings highlight the promise of delivering immunostimulatory payloads via bionic carriers,eliciting automatic in situ activation of effector immune cells in tumor microenvironment for tumor eradication.All these results provide promising prospects into the application of immunoactivator in improving cancer synergistic immunotherapy to overcome the bottlenecks in clinic.展开更多
All-silicon (Si) photodiodes have drawn significant interest due to their single and simple material system and perfect compatibility with complementary metal-oxide semiconductor photonics. With the help from a cavity...All-silicon (Si) photodiodes have drawn significant interest due to their single and simple material system and perfect compatibility with complementary metal-oxide semiconductor photonics. With the help from a cavity enhancement effect, many of these photodiodes have shown considerably high responsivity at telecommunication wavelengths such as 1310 nm, yet the mechanisms for such high responsivity remain unexplained. In this work,an all-Si microring is studied systematically as a photodiode to unfold the various absorption mechanisms.At-6.4 V, the microring exhibits responsivity up to0.53 A∕W with avalanche gain, a 3 dB bandwidth of25.5 GHz, and open-eye diagrams up to 100 Gb/s. The measured results reveal the hybrid absorption mechanisms inside the device. A comprehensive model is reported to describe its working principle, which can guide future designs and make the all-Si microring photodiode a promising building block in Si photonics.展开更多
SDF-1/CXCR4 has been recognized as one of the most relevant chemokine signaling pathways to cancer metastasis,and siRNA targeting CXCR4 may provide potential improvements to treat those highly metastatic cancers,espec...SDF-1/CXCR4 has been recognized as one of the most relevant chemokine signaling pathways to cancer metastasis,and siRNA targeting CXCR4 may provide potential improvements to treat those highly metastatic cancers,especially when combined with chemotherapy.In the present study,we constructed riboflavin-modified lipo-polyplexes to co-deliver CXCR4 siRNA and doxorubicin for cancer therapy.Doxorubicin was covalently conjugated to polyethyleneimine(PEI)with acid-cleavable hydrazine bond,and the obtained acid-sensitive conjugate was efficiently condensed with siRNA to form polyplexes,which were further coated with riboflavin-tailed lipid-membrane to prepare the lipo-polyplexes conveniently.Utilizing the fact that tumor cells overexpress riboflavin receptors,the riboflavin modification effectively enhanced uptake of lipo-polyplexes by tumor cells in a receptor-mediated manner.The riboflavin-modified lipo-polyplexes co-delivering CXCR4 siRNA and doxorubicin effectively decreased viability and invasiveness of tumor cells in vitro,and inhibited primary tumor growth and tumor metastasis in vivo.展开更多
Digital alloy In_(0.52)Al_(0.48) As avalanche photodiodes exhibit lower excess noise than those fabricated from random alloys. This paper compares the temperature dependence, from 203 to 323 K, of the impact ionizatio...Digital alloy In_(0.52)Al_(0.48) As avalanche photodiodes exhibit lower excess noise than those fabricated from random alloys. This paper compares the temperature dependence, from 203 to 323 K, of the impact ionization characteristics of In_(0.52)Al_(0.48) As and Al_(0.74)Ga_(0.26) As digital and random alloys. These results provide insight into the low excess noise exhibited by some digital alloy materials, and these materials can even obtain lower excess noise at low temperature.展开更多
基金We would like to thank the National Natural Science Foundation of China(No.81973258)the Beijing Natural Science Foundation(Nos.L202044,7202092)for funding this work.
文摘Immunotherapy has great promise in improving malignant tumor treatment.However,the efficacy of existing strategies is often limited by the immunosuppressive environment.Here,we demonstrate an in situ bionic immunoactivator,PLT-Bec1/DTA-1,with possessed natural advantages of platelets for tumor recruitment and activation,on which DTA-1(CD357 monoclonal antibody)and Bec1 were tethered as combined immune boosters.PLT-Bec1/DTA-1,as a self-triggered release repository,can deliver the pre-tethered Bec1 and DTA-1 deeply through the secretion of platelet microparticles(PMPs),thereby cooperate tacitly and exhibit superiority in immune activation of dendritic cells(DCs)and T cells via autophagy inducibility,coupled with glucocorticoid-induced tumor necrosis factor receptor(GITR)-triggered T_(Reg) suppression,remodeled the immunosuppressive network of tumor microenvironment.PLT-Bec1/DTA-1 promoted antigen presentation and T cell proliferation,and alleviated the low activity state of bone marrow-derived dendritic cells(BMDCs)in tumor suppressive environment.PLT-Bec1/DTA-1 inhibited tumor recurrence(5-and 13-fold lower of control group in tumor volume)and CD8^(+)T/T_(Reg) ratio(6.3-and 8.8-fold vs.control group)in mouse tumor model after intravenous or subcutaneous administration.Also,PLT-Bec1/DTA-1 prevented tumor colonization in lung through in situ immune activation,and was slightly superior to the combined of Bec1 and PD-L1.Our findings highlight the promise of delivering immunostimulatory payloads via bionic carriers,eliciting automatic in situ activation of effector immune cells in tumor microenvironment for tumor eradication.All these results provide promising prospects into the application of immunoactivator in improving cancer synergistic immunotherapy to overcome the bottlenecks in clinic.
文摘All-silicon (Si) photodiodes have drawn significant interest due to their single and simple material system and perfect compatibility with complementary metal-oxide semiconductor photonics. With the help from a cavity enhancement effect, many of these photodiodes have shown considerably high responsivity at telecommunication wavelengths such as 1310 nm, yet the mechanisms for such high responsivity remain unexplained. In this work,an all-Si microring is studied systematically as a photodiode to unfold the various absorption mechanisms.At-6.4 V, the microring exhibits responsivity up to0.53 A∕W with avalanche gain, a 3 dB bandwidth of25.5 GHz, and open-eye diagrams up to 100 Gb/s. The measured results reveal the hybrid absorption mechanisms inside the device. A comprehensive model is reported to describe its working principle, which can guide future designs and make the all-Si microring photodiode a promising building block in Si photonics.
基金The National Nature Science Foundation of China(Grant No.81973258 and 81673365)State Key Laboratory of Advanced Pharmaceutical Formulation with High Technology in Yangtze River Pharmaceutical Group.
文摘SDF-1/CXCR4 has been recognized as one of the most relevant chemokine signaling pathways to cancer metastasis,and siRNA targeting CXCR4 may provide potential improvements to treat those highly metastatic cancers,especially when combined with chemotherapy.In the present study,we constructed riboflavin-modified lipo-polyplexes to co-deliver CXCR4 siRNA and doxorubicin for cancer therapy.Doxorubicin was covalently conjugated to polyethyleneimine(PEI)with acid-cleavable hydrazine bond,and the obtained acid-sensitive conjugate was efficiently condensed with siRNA to form polyplexes,which were further coated with riboflavin-tailed lipid-membrane to prepare the lipo-polyplexes conveniently.Utilizing the fact that tumor cells overexpress riboflavin receptors,the riboflavin modification effectively enhanced uptake of lipo-polyplexes by tumor cells in a receptor-mediated manner.The riboflavin-modified lipo-polyplexes co-delivering CXCR4 siRNA and doxorubicin effectively decreased viability and invasiveness of tumor cells in vitro,and inhibited primary tumor growth and tumor metastasis in vivo.
基金Defense Advanced Research Projects Agency(DARPA)(W911NF-10-1-0391)Army Research Office(ARO)(W911NF-10-1-0391)
文摘Digital alloy In_(0.52)Al_(0.48) As avalanche photodiodes exhibit lower excess noise than those fabricated from random alloys. This paper compares the temperature dependence, from 203 to 323 K, of the impact ionization characteristics of In_(0.52)Al_(0.48) As and Al_(0.74)Ga_(0.26) As digital and random alloys. These results provide insight into the low excess noise exhibited by some digital alloy materials, and these materials can even obtain lower excess noise at low temperature.
